chr1-23559300-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002167.5(ID3):​c.127G>C​(p.Asp43His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D43N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

ID3
NM_002167.5 missense

Scores

10
7
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.23
Variant links:
Genes affected
ID3 (HGNC:5362): (inhibitor of DNA binding 3) The protein encoded by this gene is a helix-loop-helix (HLH) protein that can form heterodimers with other HLH proteins. However, the encoded protein lacks a basic DNA-binding domain and therefore inhibits the DNA binding of any HLH protein with which it interacts. [provided by RefSeq, Aug 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.87

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ID3NM_002167.5 linkc.127G>C p.Asp43His missense_variant Exon 1 of 3 ENST00000374561.6 NP_002158.3 Q02535
LOC124903876XR_007065537.1 linkn.282+7205C>G intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ID3ENST00000374561.6 linkc.127G>C p.Asp43His missense_variant Exon 1 of 3 1 NM_002167.5 ENSP00000363689.5 Q02535
ID3ENST00000486541.1 linkn.144G>C non_coding_transcript_exon_variant Exon 1 of 2 1
ID3ENST00000463312.1 linkn.-225G>C upstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461676
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
727148
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.83
BayesDel_addAF
Pathogenic
0.42
D
BayesDel_noAF
Pathogenic
0.37
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.94
D
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Uncertain
0.79
D
M_CAP
Pathogenic
0.42
D
MetaRNN
Pathogenic
0.87
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Uncertain
2.3
M
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-4.0
D
REVEL
Pathogenic
0.80
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0040
D
Polyphen
1.0
D
Vest4
0.90
MutPred
0.46
Loss of stability (P = 0.0734);
MVP
0.91
MPC
0.62
ClinPred
1.0
D
GERP RS
5.6
Varity_R
0.87
gMVP
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-23885791; API